Evaluating the Impact of Freespira on Panic Disorder Patients' Health Outcomes and Healthcare Costs within the Allegheny Health Network.

Panic disorder (PD) is a debilitating condition that drives medical spending at least twice as high as medically matched controls. Excessive utilization of healthcare resources comes from emergency department (ED), medications, diagnostic testing, and physician visits. Freespira is an FDA-cleared digital therapeutic that treats PD and panic attacks (PA) by correcting underlying abnormal respiratory physiology. Efficacy of Freespira has been established in prior studies. This paper reports on a quality improvement program that investigated whether treating PD patients with Freespira would reduce medical costs and improve outcomes over 12-months. Panic symptoms were assessed using the Panic Disorder Severity Scale (PDSS). Pre-and post-treatment insurance claims determined costs. At baseline, mean Clinician Global Impression (CGI-S) was 4.4 (moderately/markedly ill), mean PDSS was 14.4 and mean PA frequency/week was 2 (range 0-5). Immediately post-treatment (week 5) mean CGI-S, PDSS and weekly PA frequency declined to 2.8 (borderline/mildly ill, 4.9 (remission) and 0.2 (range 0-2) respectively, p < 0.001. 82% reported PDSS decrease of ≥ 40% (clinically significant), 86% were PA-free. One-year post treatment mean CGI-S, PDSS and PA remained low at 2.1, 4.4, and 0.3 (range 0-1) respectively. 91% had PDSS decrease of ≥ 40%, 73% were PA-free. The majority of patients were panic attack free and/or reduced their symptoms and avoidance behaviors 1-year post Freespira treatment. Mean overall medical costs were reduced by 35% from $548 to $358 PMPM (per member per month) or an annual reduction of $2280. at 12 months post-treatment. There was a 65% reduction in ED costs from $87 to $30 PMPM. Median pharmacy costs were reduced by 68% from $73 to $23 PMPM.

Error-related brain activity in pediatric anxiety disorders remains elevated following individual therapy: a randomized clinical trial.

BACKGROUND: Anxiety disorders are associated with an overactive action monitoring system as indexed by a larger error-related negativity (ERN). This study tests whether ERN magnitude changes following treatment, predicts response to treatment, and varies by treatment type. METHODS: The sample included 130 youth (9-14 years): youth with an anxiety disorder (ANX; n = 100) and healthy control (HC; n = 30) youth with no lifetime DSM-IV disorders. ANX youth were randomized to either a manualized cognitive-behavior therapy (CBT) or a comparison child-centered therapy (CCT). The ERN was assessed before and after 16 sessions of treatment and within a comparable interval for HC. Subjective ratings about making errors on the task were obtained following each testing session. The ClinicalTrials.gov identifier is NCT00774150. RESULTS: The ERN was larger in ANX than HC youth but ERN magnitude did not significantly change following treatment in the ANX youth, regardless of treatment type, and baseline ERN did not predict treatment response. Post-task ratings revealed that ANX youth worried more about task performance feedback than HC. Like the ERN, mean ratings did not significantly change following treatment. However, these ratings were not correlated with ERN amplitude. CONCLUSIONS: Findings of greater ERN in pediatric anxiety disorders are replicated in a larger sample. More importantly, findings from this randomized control trial show that a larger ERN and feeling worried about performance feedback remain unchanged following treatment and are unrelated to treatment response. Such findings suggest that action monitoring systems remain overactive in anxious youth treated with psychotherapy, suggesting the need for future investigation of whether novel complimentary cognitive and emotional training programs can modify these systems would be warranted.

A Randomized Clinical Trial Comparing Individual Cognitive Behavioral Therapy and Child-Centered Therapy for Child Anxiety Disorders.

This study compared individual cognitive behavioral therapy (CBT) and a supportive child-centered therapy (CCT) for child anxiety disorders on rates of treatment response and recovery at posttreatment and 1-year follow-up, as well as on real-world measures of emotional functioning. Youth (N = 133; ages 9-14) with anxiety disorders (generalized, separation, and/or social anxiety) were randomized using a 2:1 ratio to CBT (n = 90) or CCT (n = 43), which served as an active comparison. Treatment response and recovery at posttreatment and 1-year follow-up were assessed by Independent Evaluators, and youth completed ecological momentary assessment of daily emotions throughout treatment. The majority of youth in both CBT and CCT were classified as treatment responders (71.1% for CBT, 55.8% for CCT), but youth treated with CBT were significantly more likely to fully recover, no longer meeting diagnostic criteria for any of the targeted anxiety disorders and no longer showing residual symptoms (66.7% for CBT vs. 46.5% for CCT). Youth treated with CBT also reported significantly lower negative emotions associated with recent negative events experienced in daily life during the latter stages of treatment relative to youth treated with CCT. Furthermore, a significantly higher percentage of youth treated with CBT compared to CCT were in recovery at 1-year follow-up (82.2% for CBT vs. 65.1% for CCT). These findings indicate potential benefits of CBT above and beyond supportive therapy on the breadth, generalizability, and durability of treatment-related gains.

Trauma-focused cognitive behavioral therapy for children and families.

OBJECTIVE: This article provides information about trauma-focused cognitive behavioral therapy (TF-CBT), an evidence-based treatment for traumatized children, adolescents, and families. METHOD: The evolution of the TF-CBT model is described from the perspective of the treatment developers, including population of focus, conceptual and methodological features of the research, critical challenges and design issues that have been confronted, and how they have been addressed. Major research findings and their implications for clinical practice are also described, as well as future research challenges and directions for young researchers starting out in this field. RESULTS: The TF-CBT model has been been tested in a variety of challenging research settings and has strong evidence for improving trauma symptoms across diverse populations of traumatized children. CONCLUSIONS: TF-CBT is an effective and widely used treatment for addressing childhood trauma.

Trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing: what works in children with posttraumatic stress symptoms? A randomized controlled trial.

To prevent adverse long-term effects, children who suffer from posttraumatic stress symptoms (PTSS) need treatment. Trauma-focused cognitive behavioral therapy (TF-CBT) is an established treatment for children with PTSS. However, alternatives are important for non-responders or if TF-CBT trained therapists are unavailable. Eye movement desensitization and reprocessing (EMDR) is a promising treatment for which sound comparative evidence is lacking. The current randomized controlled trial investigates the effectiveness and efficiency of both treatments. Forty-eight children (8-18 years) were randomly assigned to eight sessions of TF-CBT or EMDR. The primary outcome was PTSS as measured with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Secondary outcomes included parental report of child PTSD diagnosis status and questionnaires on comorbid problems. The Children's Revised Impact of Event Scale was administered during the course of treatment. TF-CBT and EMDR showed large reductions from pre- to post-treatment on the CAPS-CA (-20.2; 95% CI -12.2 to -28.1 and -20.9; 95% CI -32.7 to -9.1). The difference in reduction was small and not statistically significant (mean difference of 0.69, 95% CI -13.4 to 14.8). Treatment duration was not significantly shorter for EMDR (p = 0.09). Mixed model analysis of monitored PTSS during treatment showed a significant effect for time (p < 0.001) but not for treatment (p = 0.44) or the interaction of time by treatment (p = 0.74). Parents of children treated with TF-CBT reported a significant reduction of comorbid depressive and hyperactive symptoms. TF-CBT and EMDR are effective and efficient in reducing PTSS in children.

National trainers' perspectives on challenges to implementation of an empirically-supported mental health treatment.

This study examined perceived challenges to implementation of an empirically supported mental health treatment for youth (Trauma-Focused Cognitive Behavioral Therapy; TF-CBT) and explored the potential use of technology-based resources in treatment delivery. Thematic interviews were conducted with 19 approved national TF-CBT trainers to assess their perspectives about challenges to implementation of TF-CBT and to explore their perceptions about the potential value of innovative, technology-based solutions to enhance provider fidelity and improve quality of care. These data offer some important insights and implications for training in evidence-based treatments, provider fidelity and competence, and patient engagement, particularly for those interventions targeting trauma-related symptoms among youth.

Developing a trauma focused cognitive behavioral therapy application for adolescents with problematic sexual behaviors: A conceptual framework.

Sexual abuse (SA) perpetration is a significant public health problem; SA perpetration is most likely to emerge during adolescence and youth ages 13 to 17 account for a significant portion of all child sexual abuse. While research shows that these youth have high rates of adversity, once they have engaged in problem sexual behavior (PSB), their own trauma histories are often ignored with treatment primarily focused on reducing risk for reoffending. Although sexual re-offense rates among adolescents with PSB are very low, the rates of non-sexual recidivism are considerably higher; with almost half of known youth have reoffended non-sexually, requiring development, implementation, and testing of therapeutic interventions responsive to the indicated risks and unmet needs of adolescents who have engaged in a range of problematic sexual behaviors (PSB-A) and their families. Yet, there are no empirically supported interventions designed specifically to address PSB-A with trauma histories. This article introduces how Trauma-Focused Cognitive Behavioral Therapy can be applied to PSB-A and provides implications for practice and future research.

Implementation of an evidence-based trauma-focused treatment for traumatised children and their families during the war in Ukraine: a project description.

The full-scale invasion of Ukraine by Russia in February 2022 led to an increase of traumatic events and mental health burden in the Ukrainian general population. The (ongoing) traumatisation can have a crucial impact on children and adolescents as they are especially vulnerable for developing trauma-related disorders such as Post Traumatic Stress Disorder (PTSD) or Depression. To date, these children have only very limited access to trauma-focused evidence-based treatments (EBTs) by trained mental health specialists in Ukraine. The fast and effective implementation of these treatments in Ukraine is crucial to improve the psychological wellbeing of this vulnerable population. This letter to the editor describes an ongoing project which implements a trauma-focused EBT called 'Trauma-Focused Cognitive Behavioural Therapy' (TF-CBT) in Ukraine during the war. In collaboration with Ukrainian and international agencies, the project 'TF-CBT Ukraine' was developed and implemented starting in March 2022. The project entails a large training programme for Ukrainian mental health specialists and the implementation of TF-CBT with children and their families in and from Ukraine. All components of the project are scientifically evaluated on a patient and therapist level, cross-sectionally and longitudinally, in a mixed-methods design. All together nine training cohorts with N = 133 Ukrainian therapists started the programme, all monthly case consultations (15 groups) and treatments of patients are still ongoing. Lessons learnt from this first large-scale implementation project on an EBT for children and adolescents impacted by trauma in Ukraine will help inform the field on challenges and also possibilities to expand such efforts. On a broader level, this project could be one small step in the process of helping children overcome the negative effects and experience resilience in the context of a war-torn nation.

Trauma-Focused Cognitive Behavioral Therapy for Children and Families.

Child trauma is a serious societal problem. At least one trauma is reported by two-thirds of American children and adolescents Despite children's inherent resilience, trauma exposure is associated with increased risk for medical and mental health problems including posttraumatic stress disorder, depression, anxiety, substance abuse, and attempted and completed suicide. Early identification and treatment of traumatized children can prevent these potentially serious and long-term negative outcomes.

Trauma-focused cognitive behavioral therapy with Puerto Rican youth in a post-disaster context: Tailoring, implementation, and program evaluation outcomes.

PURPOSE: Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) has not yet been systematically evaluated in the Caribbean context, particularly with Hispanic youth exposed to multiple disasters. The objective of this project was twofold: 1) to train mental health providers in Puerto Rico in TF-CBT as part of a clinical implementation project within the largest managed behavioral health organization (MBHO) on the island, and 2) to conduct a program evaluation to determine the feasibility of implementation and the effectiveness of the treatment. METHOD: Fifteen psychologists were trained in TF-CBT. These psychologists then provided TF-CBT to 56 children and adolescents, ages 5-18, in community-based mental health clinics and one primary care clinic with a co-located psychologist in Puerto Rico. The mean number of traumatic events reported by youth referred for TF-CBT was 4.11. RESULTS: Thirty-six out of 56 children enrolled in the project (64.3%) successfully completed all components of TF-CBT. Results demonstrated large effect sizes for reduction in youth-reported posttraumatic stress symptoms (PTSS) (Cohen's d = 1.32), depressive symptoms (Cohen's d = 1.32), and anxiety symptoms (Cohen's d = 1.18). CONCLUSIONS: These results suggest that it was feasible to train providers in TF-CBT, that providers were able to deliver TF-CBT in community-based settings both in person and via telehealth (due to the COVID-19 pandemic), and that TF-CBT was an effective treatment option to address trauma-related concerns for youth in Puerto Rico in a post-disaster context. This project is an important first step in the dissemination and implementation of evidence-based trauma-focused treatment for Hispanic youth and disaster-affected youth in the Caribbean.

Trauma-focused cognitive behavioral therapy for children: impact of the trauma narrative and treatment length.

BACKGROUND: Child sexual abuse (CSA) is associated with the development of a variety of mental health disorders, and Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an established treatment for children who have experienced CSA. However, there are questions about how many TF-CBT sessions should be delivered to achieve clinical efficacy and whether a trauma narrative (TN) component is essential. This study examined the differential effects of TF-CBT with or without the TN component in 8 versus 16 sessions. METHODS: Two hundred and ten children (aged 4-11 years) referred for CSA and posttraumatic stress disorder symptoms were randomly assigned to one of the four treatment conditions: 8 sessions with no TN, 8 sessions with TN, 16 sessions with no TN, and 16 sessions with TN. RESULTS: Mixed-model ANCOVAs demonstrated that significant posttreatment improvements had occurred with respect to 14 outcome measures across all conditions. Significant main and interactive effect differences were found across conditions with respect to specific outcomes. CONCLUSIONS: TF-CBT, regardless of the number of sessions or the inclusion of a TN component, was effective in improving participant symptomatology as well as parenting skills and the children's personal safety skills. The eight session condition that included the TN component seemed to be the most effective and efficient means of ameliorating parents' abuse-specific distress as well as children's abuse-related fear and general anxiety. On the other hand, parents assigned to the 16 session, no narrative condition reported greater increases in effective parenting practices and fewer externalizing child behavioral problems at posttreatment.

An Innovative Mobile Game for Screening of Pediatric PTSD: a Study in Primary Care Settings.

Childhood is a developmental period associated with high risk of posttraumatic stress disorder (PTSD). Available validated pencil-and-paper diagnostic tools can be difficult for younger children to engage with given format and length. This study investigated psychometric properties of a briefer, more interactive game version of the Child PTSD Symptom Scale for DSM-5 (CPSS-5). Participants (n = 49) were children attending primary care appointments between 8 to 12 years of age who were exposed to a DSM-5 Criterion A trauma. Participants completed the 6-item screening version of the CPSS-5 delivered in mobile tablet game format (the CPSS-5 Screen Team Game) and a self-report version of the full CPSS-5 (CPSS-5-SR) before their medical appointments. The mobile game showed adequate internal consistency (α = 0.79), was significantly positively correlated to the total CPSS-5-SR (r = .74, p < .001, n = 49), and with the total of the six identical items of the CPSS-5-SR (r = .79, p < .001, n = 49), demonstrating good convergent validity. Receiver operating characteristic (ROC) analyses revealed a cut-off score of 9 on the screening game as indicative of probable PTSD. Implementation of this screening game into primary care settings could be a low-burden method to greatly increase the detection of pediatric PTSD for referral to appropriate integrated care interventions.

Implementation of an Evidence-Based Psychotherapy for Trauma-Exposed Children in a Lower-Middle Income Country: the Use of Trauma-Focused Cognitive Behavioral Therapy in El Salvador.

Central American youth are at a high risk for experiencing trauma and related psychosocial problems. Despite this, few studies of evidence-based trauma-focused interventions with this population exist. The objective of this project was twofold: 1) to train providers in El Salvador in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) as part of a clinical implementation project within a non-governmental organization, and 2) to conduct program evaluation to determine the feasibility of implementation and the effectiveness of the treatment. Fifteen Salvadoran psychologists were trained in TF-CBT who then provided TF-CBT to 121 children and adolescents ages 3-18 in community-based locations. The mean number of traumas reported by youth was 4.39. Results demonstrated large effect sizes for reduction in youth-reported trauma symptoms (Cohen's d = 2.04), depressive symptoms (Cohen's d = 1.68), and anxiety symptoms (Cohen's d = 1.67). Our program evaluation results suggest that it was feasible to train providers in TF-CBT, that providers were in turn able to deliver TF-CBT in community-based settings, and that TF-CBT was an effective treatment option to address trauma-related concerns for youth in El Salvador. This project is an important first step in the dissemination and implementation of evidence-based trauma-focused treatment for youth in Latin American countries.

Psychotherapeutic options for traumatized children.

PURPOSE OF REVIEW: This review addresses two issues. First, it updates readers on new treatments for traumatized children. Second, it examines the breadth of target problems that current evidence-based treatments for child posttraumatic stress disorder (PTSD) effectively address in the context of current diagnostic uncertainty. Specifically, changes have been proposed to the Diagnostic and Statistical Manual for Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for PTSD and a proposal has been submitted to add a new developmental trauma disorder to optimally describe the range of outcomes experienced by traumatized children. RECENT FINDINGS: Three recently completed treatment studies are described. A review of five established child trauma treatments for PTSD, child-parent psychotherapy, cognitive behavioral interventions for trauma in schools, cognitive behavioral therapy for PTSD, structured psychotherapy for adolescents responding to chronic stress, and trauma-focused cognitive behavioral therapy documents that these treatments effectively resolve problems in multiple domains beyond the current PTSD diagnostic criteria. These domains include affective dysregulation, behavioral dysregulation, cognitive dysregulation, and relational dysregulation. SUMMARY: New treatments for children are promising for treating PTSD and some other symptoms. Current evidence-based child trauma treatments address a broad array of trauma-related difficulties.

Children's mental health care following Hurricane Katrina: a field trial of trauma-focused psychotherapies.

New Orleans school children participated in an assessment and field trial of two interventions 15 months after Hurricane Katrina. Children (N = 195) reported on hurricane exposure, lifetime trauma exposure, peer and parent support, posttraumatic stress disorder (PTSD), and depressive symptoms. Teachers reported on behavior. At baseline, 60.5% screened positive for PTSD symptoms and were offered a group intervention at school or individual treatment at a mental health clinic. Uptake of the mental health care was uneven across intervention groups, with 98% beginning the school intervention, compared to 37% beginning at the clinic. Both treatments led to significant symptom reduction of PTSD symptoms, but many still had elevated PTSD symptoms at posttreatment. Implications for future postdisaster mental health work are discussed.

Trauma-Focused Cognitive-Behavioral Therapy: The role of caregivers.

BACKGROUND: Childhood trauma exposure is unfortunately common and is associated with the development of posttraumatic stress disorder (PTSD) as well as a number of other serious medical and mental and health disorders. After experiencing trauma, children depend on their non-offending parents to believe and support them, reframe the meaning of the trauma, and to keep them safe from future harm. Parents are often negatively impacted by their child's trauma which may contribute to the child's risk for developing PTSD and related problems. Including parents in treatment may enhance child outcomes. METHODS: Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is an evidence-based child and adolescent trauma treatment model that integrally includes non-offending parents or caregivers throughout treatment (hereafter referred to as "caregivers"). This article describes TF-CBT's underlying concepts, principles and core components, as well as the role of caregiver inclusion in this model, and evaluates the extant evidence for caregiver factors in predicting TF-CBT outcomes. RESULTS: Several studies suggest that inclusion of non-offending caregivers is associated with TF-CBT outcomes, and that this may occur through enhancing caregiver support of the child and/or reducing caregivers' trauma-related maladaptive cognitions. LIMITATIONS: Few studies have evaluated whether caregiver factors served as formal treatment mediators. CONCLUSIONS: Including non-offending caregivers in TF-CBT can improve youth outcomes.

An Exploratory Trial of Cognitive-Behavioral vs Client-Centered Therapies for Child-Mother Dyads Bereaved from Terrorism.

The study was an evaluation of Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT; Cohen et al. 2017) with child-caregiver dyads who experienced the death of a loved one from terrorism, using a hybrid efficacy/effectiveness design in which there were no required minimum symptom levels. Forty children ages 4-17 years old whose fathers died in the line of duty on 9/11/2001 and their mothers participated in an RCT comparing TF-CBT and Client-Centered Therapy (CCT). At baseline, mothers' PTSD, depression, and prolonged grief symptoms were highly elevated, whereas children's were at normative levels. Using intent-to-treat analysis, condition-by-time interactions showed significantly greater symptom reduction for mothers receiving CBT than those receiving CCT. For the children, both treatments led to significant symptom improvements.

Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors.

MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines. We have determined that the kinase domain spans residues 35-382 by proteolytic cleavage. The complete kinase domain has been crystallized and its X-ray crystal structure as a complex with magnesium and ATP-gammaS determined at 2.1 A. Unlike crystals of a truncated kinase domain previously published, the crystals of the intact domain can be grown either as a binary complex with a nucleotide or as a ternary complex with a nucleotide and one of a multitude of allosteric inhibitors. Further, the crystals allow for the determination of costructures with ATP competitive inhibitors. We describe the structures of nonphosphorylated MEK1 (npMEK1) binary complexes with ADP and K252a, an ATP-competitive inhibitor (see Table 1), at 1.9 and 2.7 A resolution, respectively. Ternary complexes have also been solved between npMEK1, a nucleotide, and an allosteric non-ATP competitive inhibitor: ATP-gammaS with compound 1 and ADP with either U0126 or the MEK1 clinical candidate PD325089 at 1.8, 2.0, and 2.5 A, respectively. Compound 1 is structurally similar to PD325901. These structures illustrate fundamental differences among various mechanisms of inhibition at the molecular level. Residues 44-51 have previously been shown to play a negative regulatory role in MEK1 activity. The crystal structure of the integral kinase domain provides a structural rationale for the role of these residues. They form helix A and repress enzymatic activity by stabilizing an inactive conformation in which helix C is displaced from its active state position. Finally, the structure provides for the first time a molecular rationale that explains how mutations in MEK may lead to the cardio-facio-cutaneous syndrome.

Thermodynamics of nucleotide and inhibitor binding to wild-type and ispinesib-resistant forms of human kinesin spindle protein.

Current antimitotic cancer chemotherapy based on vinca alkaloids and taxanes target tubulin, a protein required not only for mitotic spindle formation but also for the overall structural integrity of terminally differentiated cells. Among many innovations targeting specific mitotic events, inhibition of motor enzymes including KSP (or Eg5) has been validated as a highly productive approach. Many reported KSP inhibitors bind to an induced allosteric site near the site of ATP hydrolysis, and some have been tested in clinical trials with varying degrees of success. This allosteric site was defined in detail by X-ray crystallography of inhibitor complexes, yet complementary information on binding thermodynamics is still lacking. Using two model ATP-uncompetitive inhibitors, monastrol and ispinesib, we report here the results of thermal denaturation and isothermal titration calorimetric studies. These binding studies were conducted with the wild-type KSP motor domain as well as two ispinesib mutants (D130V and A133D) identified to confer resistance to ispinesib treatment. The thermodynamic parameters obtained were placed in the context of the available structural information and corresponding models of the two ispinesib-resistant mutants. The resulting overall information formed a strong basis for future structure-based design of inhibitors of KSP and related motor enzymes.

Community treatment of child sexual abuse: a survey of practitioners in the National Child Traumatic Stress Network.

Practitioners from numerous agencies who sought training in Trauma-Focused Cognitive-Behavioral Therapy in several regional sites under the auspices of the National Child Traumatic Stress Network completed a baseline survey to describe their backgrounds, settings, practices, attitudes, and perceived outcomes with sexually abused children and youth. The results documented a range of experiences and common treatment practices, and identified contributors to practitioners' use of gradual exposure and perceived levels of positive treatment outcome. The results were not accounted for by geographic region or agency. The findings support recommendations to optimize research and training related to the dissemination of evidence-based treatments in the child abuse field.